How the genome affects our health

Jonathan Latham's article on the failure of the genome programme to identify the genes that make us disease-prone (Comment, 18 April) misses important points – some known for years, others emerging from the new science of systems biology.

First, the sorts of genes that he is writing about don't do anything on their own: they manifest their activity as proteins. Second, most proteins don't operate alone but co-operate with others in complex networks whose output is some biological driver. Third, most mutations affect the output properties of these networks not as an on-off switch but in a quantitative way. Fourth, most mutations are harmless and the basis of natural variation. Fifth, where mutations have larger qualitative effects, they can predispose us to non-infectious diseases (and we know a lot about the genetics of cancer).

The reason we find it hard to identify the genes whose mutants substantially alter network outputs is because we don't know enough about components of these networks and their dynamics. Worse, because the proteins in a network co-operate, a particular abnormal output can be due to mutations in one of several genes, as studies on heart and growth dynamics have shown. Experimentation is very difficult in this area.

What all this means is that many of the answers to the question of how we can be disease-prone do lie in the genome, but not in any simple way. It is worth pointing out that drug companies are beginning to look at how to bring under control the behaviour of aberrant networks.

Emeritus professor Jonathan Bard

Oxford

• Jonathan Latham dismisses far too readily the findings of twin studies that report levels of heritability for common disorders. If these studies are all faulty because parents treat identical twins more similarly than non-identical, why are such consistent differences found, with some disorders found to have high heritability and others low? Is it not possible that gene influences are real enough, but the gene environment interactions are too complex to be identified with present techniques (and perhaps even any that might be developed in the foreseeable future)? This possibility does not lead me to a different conclusion from Latham about research spending. We should indeed spend a far higher proportion of our research budget on clarifying the environmental side of the gene-environment equation. Where high heritability has been demonstrated, we should just be more modest in our expectations of the amount of information that studies of the environment might achieve.

Professor Philip Graham

London

• As an identical twin who feels my common inheritance with my brother is limited, I applaud the argument that being treated the same caused much of our similarities. The statistical analysis of variance techniques used in genetic studies can also be open to doubt. I've used such techniques, and they are bound to find that a few genes explain some variance and are therefore related to one or more conditions. I found, however, that when a small coding correction was made to my data the presumed relationships disappeared, only to be replaced by other variables almost as successful at prediction.

When you don't need to give any causal explanation of such relationships, it is easier to identify candidate genetic sites, and therefore further research that has to be funded. This does leave the understanding of the causes of common medical conditions in limbo, and I just hope that the recent developments in epigenetics are not now viewed too hastily as giving the answer to the problem.

Adam Pearce

Solihull

• Jonathan Latham asks: "If inherited genes are not to blame for our commonest illnesses, can we find out what is?" The answers have been known for decades, but are not genetic and have been largely unacknowledged: poor nutrition, lack of exercise, chemical pollution of our bodies and the environment, electromagnetic pollution, and the stress of living in an economically driven society. There is good reason why people who have had little contact with western ways rarely suffer from western diseases; however, if such people adopt our ways, they too become subject to our common illnesses.